Patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis have worse functional outcomes when they have brain frailty, a neuroimaging study shows. Spencer P. Loewen, PhD, from the University of Calgary, Alberta, Canada, and colleagues, reported these results in a manuscript published online Tuesday in JAMA Network Open. Brain frailty is associated with both vascular and neurological changes. Patients with injuries, such as AIS, may have a more difficult time recovering if they simultaneously have brain frailty. Neurological imaging methods are typically used to identify brain frailty: non-contrast-enhanced computed tomography (NCCT) or magnetic resonance imaging (MRI). The use of imaging to identify brain frailty markers may impact poststroke outcomes in patients with AIS who are managed with standard thrombolysis treatment. Investigators in this cohort study examined the associations between imaging-assessed brain frailty and functional outcomes in patients with AIS who underwent intravenous thrombolysis. A post hoc analysis of the Alteplase compared to Tenecteplase (AcT) open-label, investigator-led, randomized clinical trial was performed in this present study. The AcT trial took place between December 2019 and January 2022 across 22 stoke centers in Canada. Analyses occurred between July 2024 and March 2025. Reviewers were blinded to the outcome variables in the AcT trial. Brain frailty markers were defined as cortical and subcortical atrophy, white matter changes, lacunes, chronic infarctions, microbleeds, siderosis and enlarged perivascular spaces. At baseline, patients underwent NCCT and randomly received either intravenous thrombolysis with Alteplase or Tenecteplase. A few patients underwent brain MRIs after treatment. Excellent functional outcome at 90 days (measured by the modified Rankin Scale [mRS] score of 0-1) was the primary outcome in this study. A total of 1,568 patients (median age=74 years, 52.1% men) were analyzed. Patients who had higher total Fazekas scores (3-6, compared with 0) had lower chances of having a 0-1 mRS score at 90 days. Worse ordinal mRS was more likely with the presence of higher total Fazekas score, cortical atrophy and elevated total brain frailty scores. However, these were not associated with any safety outcomes. Overall, patients with AIS who receive intravenous thrombolysis treatment have worse outcomes when they also have markers of brain frailty. In an invited commentary, Amy May Lin Quek, MBBS, and Raymond Chee Seong Seet, MBBS, both from the National University Hospital and National University of Singapore, describe the details of neurodegeneration and the implications of the imaging and outcomes in this study on patients with brain frailty. “Integrating a rapid frailty assessment into every stroke evaluation can improve prognostic accuracy, tailor rehabilitation objectives to biological capacity, and mitigate therapeutic nihilism,” the editorialists concluded. Sources: Loewen SP, Singh N, Alhabli I, et al. Brain frailty and functional outcomes after thrombolysis for acute ischemic stroke. JAMA Network Open. 2025 September 30 (Article in press). Lin Quek AM, Seong Seet RC. Brain frailty score, recovery, and reperfusion safety. JAMA Network Open. 2025 September 30 (Article in press). Image Credit: Atlas – stock.adobe.com